The invention relates to the field of pure water production. In particular, the invention relates to the production of water for injection avoiding the use of distillation.
Particularly pure water is required for certain industrial uses in, for example, the pharmaceutical and electronics industries. In this context, by pure water is meant water purified for extraordinary uses, which is essentially sterile and from which inorganic and organic impurities have been removed to such an extent that preset quality requirements are fulfilled.
The quality requirements set for water are directed to its chemical and microbiological properties. The chemical quality can be properly monitored by conductivity measurement. From a microbiological point of view, the properties to be monitored are sterility and pyrogenicity. Bacteria, for example, shred cell membrane fragments into their environment. These fragments are essentially lipopolysaccharides, acting as pyrogens, i.e. fever-raising agents. These are relatively thermostable compounds, and may require high temperatures and prolonged heating periods for disintegration or loss of adverse properties. Pyrogens are removed from water in high quality distillation, and may also be removed by reverse osmosis due to the very narrow pores in the membranes used therein.
In the pharmaceutical field, the greatest purity requirements are applied to water used for injectable preparations, the so-called water for injection (WFI) grade. When water for injection is produced, the aforementioned biogenic units, which are smaller than microbes, must be removed. Methods approved for the production of WFI grade water are defined in pharmacopoeias. The 23 US Pharmacopoeia, issued in 1996, stipulates that water for injection may be produced by means of distillation or reverse osmosis. The corresponding European Pharmacopoeia allows only distillation. High grade distillation processes require substantial investments and production costs are high. Reverse osmosis is a more economical method, but often causes higher maintenance costs.
By ultrafiltration, it is possible to remove even large molecules, as pyrogens, from water. The membranes used are, however, usually sensitive to heat and harsh chemical conditions. Microbes and pyrogens must first be removed from the apparatus itself before the filtration process commences, and in addition the feed side must be cleaned, sterilized and freed of pyrogens at regular intervals during production. Most ultrafiltration equipment is badly suited for this type of use.
U.S. Pat. No. 5,104,546 discloses a method for the production of pyrogen-free water using a crossflow ultrafiltration element comprising a zirconium oxide membrane on a ceramic support. The material may be freed of pyrogens chemically, for example with nitric acid. The thermal stability of the ceramic filtration elements is also significant, and they may be repeatedly steam sterilized.
International Patent Application WO98/28060 discloses a method for manufacturing a flat, porous ceramic filter cassette, suitable for both dead-end and crossflow filtration. With proper choice of materials, the resulting filter element will have the physical and chemical resistance properties required for operation under sterilizing conditions.
U.S. Pat. No. 4,664,793 discloses a device for the production of pure water, wherein the purified water is circulated in a main circuit including a storage vessel. The water in said circuit is heat treated (60-90xc2x0 C.) in a batchwise manner when the bacterial concentration in the circuit has reached a preset threshold value. The circuit includes a dead-end filtration unit and a heat exchanger for cooling the purified water to its working temperature with external cooling water. By these means it is not, however, possible to produce, for example, water for injection, as the indicated temperature would call for a long residence time in order to reach the required sterility level.
A method according to claim 1 for the production of pure water has now been invented, comprising no periodical sterilization cycles as the continuous process comprises an integrated stage for heat sterilization of liquid water before the filtration step, and in addition the filtration itself is carried out under heat sterilizing conditions. Preferably, the pure water produced may be WFI grade.
Another objective of the invention is to provide a device according to claim 4 for the production of purified water, which device comprises as its essential components a continuously operating hot sterilization section and a filtration section wherein the filtration capacity, when required, is sufficient for producing pyrogen-free water.
Advantages and benefits of the present invention will become apparent to those of ordinary skill in the art upon reading and understanding the following detailed description of the preferred embodiments.